A major source: CAMPHOR LAUREL ROOT : Cinnamomum Camphora

C. camphora is a pest xenophyte tree species now at plague proportions
in regions such as northern NSW. They exude chemicals via their roots,
into the soil, which kills worms and other soil biota; via their leaves
which kill aquatic organisms near leaf-drop regions, and their berries
sterilise the birds which eat them. They can live for over 1200 years.
The canonical work on camphor and safrole production from this tree
was performed by Dr Teikichi Hiraizumi, President of Takasago Chem
Industry Co, Tokyo, and can be found in the essential oils work by
Guenther.

CAMPHOR OIL is obtained by steam distillation of the wood of the
camphor tree Cinnamonum camphora Sieb. (Lauraceae) growing in China,
Taiwan, Japan [and Australia, where it is classed as a noxious weed].
The main constituent of the crude oil is camphor (ca. 50%) which can
be separated by cooling and centrifugation.

Fractionation of the mother liquor gives two oils:1) White camphor oil is the first distillation fraction (ca
20% of the crude camphor oil). It is a colourless or nearly colourless
liquid with a cineole-like odour.

2) Brown Oil of camphor is a fraction with a boiling point
higher than that of camphor (ca. 20%) It is a pale yellow to brown
liquid with the odour of sassafras oil.

The oil contains more than 80% safrole and, like Brazilian sassafras
oil, is therefore used as raw material for the production of piperonal
via isosafrole. Camphor oils with a high safrole content can also
be obtained by steam distillation of the wood of Cinnamonum parthenoxylon
Nees.

Three Varieties of camphor oils are produced.

Formosan Camphor oils

camphor-linalool and camphor-safrole types.

Japanese Camphor oils

camphor-safrole types.

Chinese Camphor oils

cineole-terpineol-camphor (Apopin Oil) type.

Camphor oil "true" is produced by the steam distillation
of the wood, rootstumps and branches of the type of Cinnamonum Camphora
known as Hon-Sho, which grows in Formosa and Japan. [Ed Note: Hon-Sho
oil holds 18.1% safrole)

Along with the crude oil comes a solid, partly crystalline mass of
crude camphor. The oil is separated from the crude camphor by filterpressing.
This yields crude camphor oil. The crude oil is subsequently fractionally
distilled under vacuum, and yeilds another 50% of crude camphor. The
remaining 50% of
filterpressed crude camphor oil is now free of camphor. It contains
light terpenes, cineole, safrole, terpineol, sesquiterpenes, and sesquiterpene
alcohols. These are separated into various fractions known as:

White Camphor oil

The light fraction, containing cineole and monoterpenes.

Brown Camphor oil

The medium heavy fraction containing up to 80% of
safrole and some terpineol.

[Extended Monograph]
Brown oil of camphor is the medium heavy fraction from vacuum distillation
of the camphor-free oil (aka white oil, filterpressed and camphor-free).
Brown camphor oil amounts to 6 or 7 percent of the total oil, or 20-22%
of the decamphorised oil. Brown oil is produced almost entirely in
Formosa and Japan, from the Hon-Sho type of cinnamomum camphora, the
camphor tree.

This fraction is most interesting from the perfumer's point of view.
Its main constituent is safrole, and the redistilled brown camphor
can be used directly in soaps for its magnificent masking effect.
The safrole can be isolated from the oil and used as a starting material
for heliotropine, vanillin and other perfume materials. Terpineol
is also separated during the safrole-isolation and serves as is or
may be transformed into terpinyl esters.

An artificial sassafras oil, "Oil Camphor Sassafrassy"
is also produced from the brown oil by rectification and adjustment
of the content of safrole, terpenes, etc.

JUNIPER leaves - juniper virginiana

Table below: representative volatile leaf oil composition for junipers
(J. virginia var virginiana (USA), eluted from a DB-5 gas chromatography
column. Data expressed in % of total oil, the oil derived from steam
distillation of the FOLIAGE. (so no digging-up of the roots is required).

This gave us a list of approximately 140 distinct molecules which
came off the column, I left most of them off.

The significant numbers are marked in red

RT(s)

Compound

%

B.P. (deg C) from Merck,
12th edn.

319

alpha-pinene

1.4

bp20:52.5 bp760:155-156

379

sabinene

6.7

No Listing

408

myrcene

0.9

beta from: bp10:44

481

limonene

18.9

bp763:175-176

608

terpinolene

0.5

No Listing

632

linalool

4.4

(dl) 194-197

734

camphor

3.7

mp:179 bp204

789

borneol

0.8

mp:(d)208 (l):204 bp:(d) 212:(l) 210

820

4-terpineol

1.5

bp:206-219 (d, l, and dl)

1101

safrole

10.9

mp:~11 bp:232-234

1229

cis-isosafrole

6.7

mp:~8.2 bp760:253 bp100:179.5

1403

methyleugenol

2.9

No Listing

1700

delta-cadinene

0.8

bp9:124

RT = retention time on the DB-5 column.

I gather this tree is known as the Red Cedar, though I think there
are probably several trees which come under this moniker so there
is room for confusion. It is also supposed to be the source of Red
Cedarwood Oil, though the safrole content of this is unknown. Cedarwood
oil is used for immersion
lenses in high-magnification microscope work.

Note: the incompetants at AUROMA
Australia will supply you with the leaf oil of the communis species
when you ask for the virginiana type. Ellisons of Nowra sell the seeds
to this plant, which have reliably germinated.

Sassafras

There are numerous members of the sassafras family.

A guide to the safrole content sassafras oil is its congealing point.
Accuracy is approximatey 2%

% Safrole

Congealing Point °C

100

11.0

90

7.5

80

4.6

70

1.7

60

-1.3

(ex: Planta Medica. 61(6):574-575, 1995 Dec.ISSN 0032-0943)

Abstract: The root bark of Sassafras albidum (Nuttall) Nees Lauraceae)
was extracted at room temperature with hexane and chloroform as solvents.
The isolated essential oils were analyzed with GC and GC/MS. Thirty
compounds were identified, nine of which have not been previously
reported from this species. The major compounds were safrole (85%),
camphor (3.25%), and methyleugenol (1.10%). Ten sesquiterpenes were
also identified.

Australian Native Tree Species Bearing Safrole

From the file: NATIVSAF.DOCContent: List of Australian native trees alleged to contain
safrole. Descriptions are supplied to assist recognition.

Page: 72 Fig: N/A Ref:21Species: Zieria SmithiiFamily: RutaceaeSynonyms: NoneVernacular names: Sandfly Zieria, Sandfly Bush, Lanoline Bush,
`Stinkwood'Appearance: A small to tallish shrub with opposite leaves.
Each leaf consists of three nearly hairless leaflets which vary from
narrow to broadly egg-shaped, and are tapered at both ends, 2.5-5cm
long. When crushed they exhibit a strong odour. Small 4-petalled white
flowers occur in loose clusters in the forks of leaves in Spring.Habitat: Common in sandy forest or cleared areas along the
east coast from Victoria to Northern Queensland.Active Con: Foliage essential oil. Safrole, elemicin and methyleugenol
may be present in major amounts in the steam-distilled oil.

Page: 80 Fig: N/A Ref: 16Species: Atherosperma moschatumFamily: Atherospermae (Maybe Monimiaceae)Synonyms: NoneVernacular names: Sassafras (Native, Black, Victorian, Southern)Appearance: Small to medium tree, aromatic in all its parts.
Young branches, flowers and the underside of the leaves are brownish
or greyish hairy. Its opposite leaves are rigid and tapered at both
ends, sometimes with toothed margins. Leaves are often arranged in
one plane, length from 3-10cm. Solitary summer flowers in leaf forks.Habitat: In rainforest and moist gullies of Tas, Vic and N.S.W.
as far north as the Barrington Tops district.Active Con: The bark oil probably contains safrole. Also numerous
alkaloids.Author notes: This species can be found with effort near the
Upper Causeway at Royal National Park, and also on the scree slopes
of Wombarra, north of Wollongong, around the remains of the coal mine
workings and impending drainage works.Distillation: The leaves yield no safrole when dried, chopped
finely and steam distilled, and only a miniscule amount of ti-tree
(Maleleuca tree) - like oil.

Species: Doryphora aromaticaFamily: AtherospermataceaeSynonyms: Daphnandra aromaticaVernacular names: Sassafras (Grey, Northern Grey, Net Sassafras,
Cheedingnan (Barron river)).Appearance: A tree up to 35m high exhibiting large pustules,
up to 6mm across. Both the yellow wood and the bark are very aromatic.
Young branchlets are sometimes 4-angled. Young shoots and flowers
are hairy. Leaves are opposite, elliptical, tapered at both ends,
6-15cm long and have toothed margins. Flowers are borne in the upper
leaf forks at the end of the branchlets. Fruits are club-shaped or
tubular, 1.5-2.5cm long. they split lengthwise when mature and release
several tufted seeds. Differs from Daphnandra micrantha by being more
aromatic and having less-toothed leaves as well as a larger plume
of hairs on the seed.Habitat: In the rainforests of northern Queensland.Active con: The bark oil contains a volatile oil rich in safrole,
plus several alkaloids.

Page: 86 Fig: N/A Ref: 16Species: Doryphora sassafrasFamily: AtherospermataceaeSynonyms: noneVernacular names: Sassafras (NSW, caalang (Illawarra), boobin
(North NSW), tdjuendegong (Brisbane Water).Appearance: A large tree 20-30m high, exceptionally 40m. Opposite
leaves are dark green and glossy, with coarsely toothed edges showing
prominent veins on the underside. They are eliptical, tapered at both
ends, narrowed at the base and 4-10cm long. Young shoots are silky
hairy. Its short-stalked, starlike flower (usually three together)
are pure white and occur in leaf forks, forming a stark contrast to
the dark shining foliage. Flowers in early spring.Habitat: In the rainforests of the eastern districts of NSW
and south Queensland. It occurs in the blue mountains west of Sydney
and as far west as the Jenolan caves.Active con: The leaves contains an essential oil rich in safrole,
plus several alkaloids.

Page: 151 Fig: N/A Ref: 107, 108Species: Cinnamomum oliveriFamily: LauraceaeSynonyms: noneVernacular names: Sassafras (Oliver's, camphorwood).Appearance: A tall tree up to 45m high, with a brown, nodular
bark, very fragrant when cut. Its opposite leaves are narrow and tapered
at both ends, glossy above and much paler below, 20cm long and 3.5cm
broad. Velvety, cream coloured flowers occur in bunches 15-20cm long
in upper leaf forks or at then end of branchlets. Fruits are oval
berries, 12mm long, containing a single seed, sometimes irregular
in shape owing to numerous galls. Flowers in late spring to early
summer. The similar Beilschmiedia obtusifolata has much broader leaves.Habitat: In the rainforests of northern NSW and southern Queensland. Active con: The bark contains an essential oil rich in safrole,
plus several alkaloids along with camphor, methyleugenol, or eugenol
depending on the species. It is not certain that the Australian authorities
would go on an enviropogrom in order to destroy these plants. They
have attempted to suppress marijuana with only limited success. It
is unlikely therefore that they can successfully suppress sassafras
trees. Incidentally, yes you can find large stands of sassafras trees
near a town called Sassafras, NSW.

Safrole is also informally known as shikimole, by some bizarre phonetic
allusion to shikimic acid, a biological precursor to several aromatic
compounds, but which is chemically quite distant to safrole. The Japanese
name for Illicium religiosum Sieb et. Zucc is "Shikimi"

Smell

Safrole's smell has been variously described in terms of other molecules.
Safrole probably interacts with the same olfactory G-coupled receptors
as the volatiles in the anise plant, and this makes sense insofar
as some of the components in the oil of anise are structurally similar [but not the same as -- Erowid]
to safrole. It is accurately described as a candy-shop odour. Go into
a place which sells more sugary things than chocolatey things and
take a deep whiff. It is also reminiscent of ginger. It has been described
as smelling like MDMA, anise, rootbeer, sassafras oil, MDA, mCPP or
sodium lactate. Halo-derivatives of
safrole are said to have similar smells to the parent molecule. Safrole
is conspicuously absent from the Sigma-Aldrich Flavours and Fragrances
catalog. Some useful derivatives of safrole (piperonal "sweet,
floral", piperonyl acetate, "cherry, strawberry", piperonyl
acetone and piperonyl isobutyrate "fruity, berry") are present,
however.

Structural diagrams

Toxicity

LD50 in rats is 2.35g/kg. It is mainly metabolised
by the cytochromes P450. Neither sassafras nor the oil should be taken
internally. The use of herb teas of sassafras may lead to a large dose
of safrole. The use of safrole in foods has been banned because of carcinogenic
and hepatotoxic risks. The use of safrole in toilet preparations is
also controlled. A 47 year old woman experienced 'shakiness', vomiting,
anxiety, tachycardia and raised blood pressure following ingestion of
a potentially fatal dose of sassafras oil (5mL). Treatment was symptomatic
following the use of activated charcoal.See: Grande GA, Dannewitz SR,
Symptomatic Sassafras Oil Ingestion,
Vet. Hum. Toxicol 1987 29 447
Recognized Carcinogen P65, Suspected Gastrointestinal or Liver Toxicant,
Kidney Toxicant, Neurotoxicant, Reproductive Toxicant. More hazardous
than most chemicals in 6 out of 7 ranking systems. At least 8 covalent
adducts are formed when calf thymus DNA is incubated with safrole-2',3'-oxide,an
oxygenated metabolite of safrole in vitro. However, no corresponding
adducts are formed with liver DNA when whole animals are exposed to
safrole 2',3'-oxide, or safrole itself. Although safrole 2',3'-oxide
is readily formed in vivo, and is sufficiently reactive to covalently
bind to DNA, it is probably not a factor in the in vivo genotoxicity
of safrole. Tox. Letters. 75(1-3):201-207, 1995 Jan. ISSN 0378-4274

Safrole FTIR Spectrum

Applications

Safrole was used for decades in perfumes and medicines
until in the 1960's. Its primary industrial application was conversion
to isosafrole, a precursor to a dye called heliotropin and vanillin,
a flavour molecule. In the 1990s it was listed, along with isosafrole,
on the prohibited import regulations list, due to its application as
a precursor in the synthesis of banned psychoactive methamphetamines.
It is still used in the preparation of the following pharmaceutical
products:
Humexinal, Inhalador Vicks, Linimento Klari, Linimento Walderr, Zam-Buk
and Vegebom du Dr Miot, though in small quantities. Piperonyl butoxide,
which is used as a synergist in aerosol pesticides, is probably synthesised
from a safrole-derived feedstock.

3) Safrole extraction and refinement

Isolating Methods

Soxhletting the root bark of cinnamomum camphora (camphor laurel),
or probably parts of other plants (see below) with distilled ethanol,
or hexane and chloroform, yields most of the available safrole, and
is cheap and effective. The solvents can be evaporated off or reclaimed
by distillation.
Dealing with the impurities in the soxhlet extract is another matter.
Steam distillation from bulk plant material is also reported to work.

Refinement methods from oil

Cool the oil or the safrole-containing fraction of the oil, to
at least -12°C. Safrole will crystallise.

Where safrole may be contaminated by oily constituents in an essential
oil as in red camphor oil, the method of Ikeda and Takeda (a) may
be employed advantageously to determine the safrole by reparation
of the addition product with mercuric acetate and sodium chloride
in dilute acetone. The precipitate so formed should be filtered in
a Gooch funnel and weighed, and used with a correction factor to define
the percentage of safrole in the sample. This complex hydroxychloride
of safrole [C10H10O2(OH)HgCl] according to Tsukamoto (b) is readily
decomposed to regenerate safrole either by sodium sulfide and zinc
in potassium hydroxide; or hydrochloric acid. The oxychloride melts
at 141-142°C according to Fujita (c).

4) Derivatives and characterisation

Safrole will convert to allylpyrocatechol when heated
with phosphoric acid. Safrole is oxidised to piperonylic acid (mp 238°C)
by the action of potassium permanganate in aqueous acetone. Some piperonylacetic
acid (mp 87-88°C) is also produced. Safrole is oxidised to piperonal
(heliotropin, mp 38°C) by the action of potassium dichromate and dilute
sulfuric acid. Safrole isomerises to isosafrole when heated with alkalis.
See also step (3) in isolation, above.

Isosafrole (120-58-1)

Isosafrole is technically a member of the styrenes and
polymerises under the influence of acids. It is soluble in ethanol,
ether, benzene and is steam-volatile. It shares safrole's empirical
formula and molecular weight. Isosafrole exists in two isomeric forms,
the cis- isomer and the more energetically favourable trans-isomer.
Warming converts the cis-form to the trans-configuration. Isosafrole
is not as widely distributed in nature as safrole. It is best purified
via a picrate derivative, the trans- isomer of which has mp 74.75°C.
The picrate cis- isomer melts at 68.5°C.
Cis-isosafrole boils at 253°C at 760mmHg; 179.5°C at 100mmHg.
Trans-isosafrole melts at 6.7-6.8°C and boils at 247-247°C.
Trans-isosafrole has a density of 1.122g/cc.

Halo-adducts

Tribromosafrole dibromide,
("pentabromosafrole") is prepared by dissolving 0.41g of safrole
in 3mL of ethanol, and treatment with 2g bromine for eight minutes.
Heat for 15 minutes on a water bath, then cool. Recrystallise the solid
from 7mL of benzene. Needles, m.p. 169-170°C.

The 2-bromo-product,
the propyl arm is substituted with Br at the 2 position, from reaction
with HBr, is in Beilstein on p228 of _19_, 3/4, I. This bromo material
is reported to have a density between 1.5614 and 1.5640, with the following
boiling points for given pressures in mmHg:

Markownikov Br-product
Getting this Markownikov depends on the absence of peroxides in the
precursor materials, such peroxides can be sequestered out by the addition
of a small quantity of hydroquinone (used in photography) to the reaction.
The 2-iodo-equivalent of the above, C10H11O2I is produced with HI under
DMSO.

5) Non regulated commercial sources

Not tested: your mileage may vary.
Why would you want a tonne of safrole? Why, for synthesis into piperonyl
butoxide for use in insecticidal preparations, or manufacture of dyes,
flavours, etc, of course, and you're too lazy to extract it from plants.
Oils to order include:
Juniper (var. virginialis) Oil, Sassafras Oil, Brown Oil of Camphor,
Nutmeg Oil.

Prices quoted are for reference only in US$ on fob basis valid on 1st
August, 1996. Please contact us for firm quotations. Shipments can be
made by sea/air, minimum order US$5000. Quantity discounts available.
E-mail Questions and comments to orient@orc.com.hk 1995-97

7) Addenum

(Addition by "Indole"):

Chenopodium ambrosioides var. anthelminticum (Wormseed) (flowering
plant, % unknown)
(this one is an oil that is restricted in most countries, apparantly
due to it's high ascaridole (up to 80%) content)Note by MescalToad: ascaridole is an unstable (even explosive)
peroxide.

These are additions to the species already mentioned:

Cananga odorata (add. var. macrophylla, other variety doesn't seem
to have safrole/isosafrole), also Cananga odorata appears to have safrole,
never seen info saying it had isosafrole...

Also, you could probably change Illicium verum from (Star Anise...
disputed) to (fruit, unknown) or (fruit, low%) as the same ref. I keep
mentioning has info on this one...although it is low... DISPUTED

Anonymous:

Just thought you might like to add some info onto your safrole FAQ
sheet on your site. The Australian botanicals, southern sassafras and
ziera smiithi have no safrole in their roots, bark, trunks or foliage.
Southern sass has nothing worth mentioning whilst smiithi contains lots
of methyl eugenol, which is where the confusion started I believe, the
text 'poisionous plants of Australia' is fraught with errors and as
much of the info in the current Safrole FAQ is lifted directly from
this hence the errors. This will save readers much time I believe as
I have wasted heaps of time collecting , seperating and steam distilling
all the bits. The methyl eugenol's existence was confirmed through FTIR
and NMR library matches so there is no doubt to the accuracy of this
info. The only assumption I am making is that maybe safrole only seasonally
appears in these species, as my samples were all collected in winter/spring.

Notes:

Illicium verum - Star Anise - Note : RA points out
that research has shown star anise contains no or very low levels of safrole and high levels of anethole,
a structurally similar oil. If synthetic techniques designed for safrole are used on anethole, dangerously
different final chemicals can result, such as PMA instead of MDMA. (Added by Erowid July 2007)